Significance: Malaria parasites infect about a billion individuals and cause up to 2 million deaths per year. A wide variation in pathology caused by Plasmodium falciparum needs clearer understanding. Tools which allow patient-specific analysis of cytoadhesion preferences of the parasite and splenic management of red cells would be most helpful. New approach: We have shown that microfluidic tools are particularly well-suited for such challenges because the devices require very small sample volumes, they are versatile, portable, and cheap. Principles to Practice: Our lab-based exploratory studies have led to improved device design and fabrication, sample management, and important malaria-specific questions. We now wish to implement the technology in Africa, the site of malaria pathology. In Specific Aim 1, microfluidic devices will be redesigned to capture small numbers of mammalian cells and to test adherence to infected erythrocytes from the same patient. In Specific Aim 2, wedge-shaped devices will measure the deformability limits of uninfected and infected RBCs will be complemented with new devices to measure propensity for+ cell lysis under controlled fluid pressures. In Specific Aim 3, we will implement this new technology at a field site in Africa. First, infected patent RBCs will be compared to cells from laboratory culture. For this, left-over patient blood (<10 ul) will be accepted from hematocrite samples collected by others for their own activities in Malawi. The patients will be anonymous to us and samples (which are normally discarded) will be discarded by us immediately after our measurements. Value: The tools and experiences from this R21 application will be of general use to the malaria community, both for future basic and clinical research related to pathogenesis. PUBLIC HEALTH RELEVANCE: Malaria causes up to 2 million deaths per year. Our understanding of the cellular pathology caused by Plasmodium falciparum, and the natural variations in disease progression, is expected to be greatly enhanced using microfluidic devices that measure cytoadhesion properties and deformability properties of infected erythrocytes from individual patients.